The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.
K-rasG12V transformation leads to mitochondrial dysfunction and a metabolic switch from oxidative phosphorylation to glycolysis
Open accessAbstract
Increased aerobic glycolysis and oxidative stress are important features of cancer cell metabolism, but the underlying biochemical and molecular mechanisms remain elusive. Using a tetracycline inducible model, we show that activation of K-rasG12V causes mitochondrial dysfunction, leading to decreased respiration, elevated glycolysis, and increased generation of reactive oxygen species. The K-RAS protein is associated with mitochondria, and induces a rapid suppression of respiratory chain complex-I and a decrease in mitochondrial transmembrane potential by affecting the cyclosporin-sensitive permeability transition pore. Furthermore, pre-induction of K-rasG12V expression in vitro to allow metabolic adaptation to high glycolytic metabolism enhances the ability of the transformed cells to form tumor in vivo. Our study suggests that induction of mitochondrial dysfunction is an important mechanism by which K-rasG12V causes metabolic changes and ROS stress in cancer cells, and promotes tumor development.
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Cites
Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation
Vander Heiden, M. G., Cantley, L. C., & Thompson, C. B. (2009) · Science · doi:10.1126/science.1160809 · Cited by 16,197
Trachootham, D., Zhou, Y., Zhang, H., Demizu, Y., Chen, Z., Pelicano, H., Chiao, P. J., Achanta, G., Arlinghaus, R. B., Liu, J., et al. (2006) · Cancer Cell · doi:10.1016/j.ccr.2006.08.009 · Cited by 1,080
Cited by
Energy metabolism of cancer: Glycolysis versus oxidative phosphorylation (Review)
ZHENG, J. (2012) · Oncology Letters · doi:10.3892/ol.2012.928 · Cited by 963
Kamphorst, J. J., Cross, J. R., Fan, J., de Stanchina, E., Mathew, R., White, E. P., Thompson, C. B., & Rabinowitz, J. D. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1307237110 · Cited by 726
Genetics and biology of pancreatic ductal adenocarcinoma
Ying, H., Dey, P., Yao, W., Kimmelman, A. C., Draetta, G. F., Maitra, A., & DePinho, R. A. (2016) · Genes & Development · doi:10.1101/gad.275776.115 · Cited by 527
Hu, K., Li, K., Lv, J., Feng, J., Chen, J., Wu, H., Cheng, F., Jiang, W., Wang, J., Pei, H., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci124049 · Cited by 404
Self-citationEnergy metabolism in health and diseases
Liu, H., Wang, S., Wang, J., Guo, X., Song, Y., Fu, K., Gao, Z., Liu, D., He, W., & Yang, L.-L. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02141-x · Cited by 399
Metadata
- Authors
- Hu, Y., Lu, W., Chen, G., Wang, P., Chen, Z., Zhou, Y., Ogasawara, M., Trachootham, D., Feng, L., Pelicano, H., Chiao, P. J., Keating, M. J., Garcia-Manero, G., & Huang, P.
- Venue
- Cell Research
- Published
- 2011-08-30
- Volume
- 22
- Issue
- 2
- Pages
- 399-412
- ISSN
- 1001-0602 (ISSN-L)
- 1748-7838
- OpenAlex
- W2166087647
- Cited by
- 304
- References
- 2
- FWCI
- 5.99
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Hu, Y., Lu, W., Chen, G., Wang, P., Chen, Z., Zhou, Y., Ogasawara, M., Trachootham, D., Feng, L., Pelicano, H., Chiao, P. J., Keating, M. J., Garcia-Manero, G., & Huang, P. (2012). K-rasG12V transformation leads to mitochondrial dysfunction and a metabolic switch from oxidative phosphorylation to glycolysis. Cell Research. https://doi.org/10.1038/cr.2011.145
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